Patterns of indolence in prostate cancer (Review)

Abstract

Although prostate cancer is a major cause of cancer-related mortality worldwide, most patients will have a relatively indolent clinical course. Contrary to most other types of cancer, even the diagnosis of locally advanced or metastatic disease is not always lethal. The present review aimed to summarize what is known regarding the underlying mechanisms related to the indolent course of subsets of prostate cancer, at various stages. The data suggested that no specific gene alteration by itself was responsible for carcinogenesis or disease aggressiveness. However, pathway analysis identified genetic aberrations in multiple critical pathways that tend to accumulate over the course of the disease. The progression from indolence into aggressive disease is associated with a complex interplay in which genetic and epigenetic factors are involved. The effect of the immune tumor microenvironment is also very important. Emerging evidence has suggested that the upregulation of pathways related to cellular aging and senescence can identify patients with indolent disease. In addition, a number of tumors enter a long-lasting quiescent state. Further research will determine whether halting tumor evolution is a feasible option, and whether the life of patients can be markedly prolonged by inducing tumor senescence or long-term dormancy.

Double trouble for prostate cancer: synergistic action of AR blockade and PARPi in non-HRR mutated patients

“…Hereby, the question regarding the effect of cells in a quiescence state arises. This quiescence state is known to be important for tumor cells to develop new evasive mechanisms through genomic changes ( 49 , 50 ). The effect of PARPi in quiescent PCa cells is currently not known.…”

Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer

“…Pathogenic mutation in the DDR genes BRCA1/2 and ATM status differs between risk for aggressive and indolent PCa and is linked to a younger death age and a shorter survival period ( Na et al, 2017 ). According to research, while some people have aggressive cancers that metastasize and result in disease-related death, many with indolent tumors can be successfully treated with early therapy or monitored ( Sakellakis et al, 2022 ). Furthermore, studies conducted in various contexts with various populations have demonstrated that homologous recombination repair (HRR) and mismatch repair genes, which are mutated in a high proportion of patients, are involved in aggressive PCa biology ( Lukashchuk et al, 2023 ).…”

Novel Multiparametric Magnetic Resonance Imaging-Based Deep Learning and Clinical Parameter Integration for the Prediction of Long-Term Biochemical Recurrence-Free Survival in Prostate Cancer after Radical Prostatectomy

“…Accurate prediction of post-RP BCR requires long-term follow-up (>10 years) owing to the high variability of BCR events and PCa’s slow-growing and often indolent nature [ 37 , 38 ]. More importantly, the characteristics of PCa exhibit regional and ethnic variations, suggesting that race- and nation-specific characteristics of PCa should be considered for developing a more accurate prediction model.…”